Tumor-associated antigens serve as potential targets for the immune system of the host and may play a role in establishing the malignant phenotype of the tumor cell. The long-term objective of the proposed research is to understand the mechanisms by which the tumor cell regulates the expression of its tumor associated antigens. To accomplish this aim we will study several surface antigens in detail and attempt to understand the mechanism of action of the genes involved in their biosynthesis and in the regulation of their expression on the cell surface. Mutants which fail to express specific antigens on their cell surface will be isolated from murine lymphomas and from cell lines expressing assayable biological functions. Somatic genetic analysis will be used to establish the number, dominance, and nature (structural or regulatory) of genes involved in antigen biosynthesis and control. Hybrids between tumor cells representing different states of normal differentiation will also be studied to gain insight into the mechanisms regulating the expression of cell surface antigens.